The incidence of malignant melanoma and malignant melanoma deaths have greatly increased in the United States. By the year of 2000, the life time risk for developing cutaneous malignant melanoma is predicted to be at about one in 90. There is an urgent need to further understand key factors in the pathogenesis of malignant melanomas. Malignant melanoma is deadly, because of the high tendency to spread to other organs. Unfortunately, similar to all other cancers the molecular mechanism of metastasis of melanomas remains elusive. The goal of this project is to begin to understand how a localized melanoma spreads to other organs and cause death. The malignant form of human skin melanoma expresses a high amount of a surface protein, called MUC18. This protein is normally present only in smooth muscle cells and in the cells of the inner linings of blood vessels. The protein appears to play a role in cell to cell communication and attachment. It has been suggested that MUC18 is involved in the progression of human melanomas. Definite proof for the direct contribution of the MUC18 protein in potentiating metastatic ability of melanomas however remains obscure. The immediate goal of this project is to find out whether this protein actually facilitates spreading of melanoma cells to other tissues in a mouse model. Eventually, new knowledge learned from this work should be applicable for developing an effective immuno-therapeutic cure for this fatal human skin cancer.